Cetuximab effects depend on treatment starting time. A: Quantification of saphenous nerve area in WT (white bars) and CNPase-hEGFR (black bars) mice. Untreated CNPase-hEGFR nerves were significantly larger than WT (P < 0.001, n = 6). Nerves of CNPase-hEGFR mice treated with cetuximab in the 6 × 2 group were also significantly larger than WT (P < 0.01, n = 6). Area of nerves from CNPase-hEGFR mice treated with cetuximab for 2 or 6 weeks beginning at birth did not differ significantly from WT mice (0 × 2: P = 0.36, n = 5; 0 × 6: P = 0.32, n = 6). Nerve area was intermediate in EGFR+ mice treated with cetuximab beginning at 1, 2, or 3 weeks of age. B: Quantification of nuclear counts in WT (white bars) and CNPase-hEGFR (black bars) nerves. Graph shows average number of nuclei per section. Nuclei counts were significantly higher in untreated CNPase-hEGFR nerves (P < 0.001, n = 6) and 6 × 2 CNPase-hEGFR nerves (P < 0.01, n = 6) compared to WT counterparts. Nerve nuclei counts of CNPase-hEGFR mice treated with cetuximab for 2 or 6 weeks beginning at birth did not differ significantly from WT (0 × 2: P = 0.1, n = 5; 0 × 6: P = 0.28, n = 6). Nerve nuclei counts were intermediate for CNPase-hEGFR mice in the 6 × 6, 3 × 2, 2 × 2, and 1 × 2 groups. C: Quantification of mast cell counts in WT (white bars) and CNPase-hEGFR (black bars) nerves. Graph shows total number of mast cells per nine sections. Mast cell numbers were significantly higher in untreated CNPase-hEGFR nerves (P < 0.001, n = 6) compared to untreated WT nerves and in all treatment paradigms that did not begin at birth. Mast cell numbers in CNPase-hEGFR nerve from mice treated with cetuximab for 2 or 6 weeks beginning at birth did not differ significantly from WT (0 × 2: P = 0.36, n = 5; 0 × 6: P = 0.32, n = 6). D–F: Sciatic nerve tissue sections from 3-month-old mice stained with Gomori’s trichrome staining. D: WT mouse nerve shows normal staining with little collagen (green). E: Untreated CNPase-hEGFR nerve has more collagen than WT mouse. F: CNPase-hEGFR nerve treated with cetuximab (0 × 6) shows collagen similar to WT.